Cost-Effectiveness Analysis of Myopia Progression Interventions in Children

Key Points Question What is the most cost-effective strategy for controlling myopia in children? Findings This cost-effectiveness analysis compared 13 myopia progression interventions for children using a Markov model. Over 5 years, atropine, 0.05%, and outdoor activity were cost-effective, with an incremental cost-effectiveness ratio of US $220 per spherical equivalent reduction for atropine, 0.05%, and a cost savings of US $5 per spherical equivalent reduction for outdoor activity; red light therapy, highly aspherical lenslets, and orthokeratology could also be cost-effective, although at higher costs. Meaning These results suggest that the use of certain interventions may help reduce myopia progression in children in a cost-effective way.


Introduction
Myopia (nearsightedness) is a major cause of visual impairment.Worldwide, approximately 153 million individuals older than 5 years have visual impairment due to uncorrected refractive errors, and of these, 8 million are blind. 1It has been estimated that the prevalence of myopia will increase from 2.6 billion in the year 2020 to 4.8 billion by the year 2050 (49.8% of the world's population). 2e high and rising prevalence of myopia has become a major global health concern because of the potential long-term complications, including cataracts, myopic macular degeneration, glaucoma, and retinal detachments. 3Myopia, in particular high myopia, substantially affects the social, educational, and economic aspects of life. 4e health cost associated with myopia is high mainly due to the direct costs of myopia correction.The estimated annual cost of myopia in US dollars was approximately $4 to $7 billion in the United States 5 and $25 to $755 million in Singapore. 6,7The cost increases when myopia-related morbidities cause visual impairment and blindness.For instance, patients with myopic choroidal neovascularization incurred a direct medical cost of €1629 (US $1743) more than those without. 8In 2015, the global potential productivity loss due to uncorrected myopia and myopic macular degeneration in US dollars was $244 billion and $6 billion, respectively. 9e efficacy of different interventions to halt or slow myopia progression has been evaluated.0][21][22][23][24] Higher doses of atropine were the most efficacious modality, while orthokeratology, pirenzepine, peripheral defocus modifying contact lenses, cyclopentolate, and prismatic bifocal spectacle lenses had moderate effects. 25wever, the cost-effectiveness of these interventions requires a thorough evaluation. 26To date, only 1 study has examined the cost-effectiveness of photorefractive screening in 11-year-old children followed by treatment with atropine eye drops, 0.01%, for the children who have positive screen results for myopia. 27The knowledge gap on the cost-effectiveness of myopia interventions has to be addressed to provide pivotal data for health policy planning and maximize health outcomes under limited resources. 5,28A comprehensive cost-effectiveness analysis that examines a broad spectrum of myopia control interventions (ie, pharmacological, spectacles, and contact lenses) is required.Therefore, this study aimed to determine the cost-effectiveness of the current myopia progression interventions in 10-year-old children.

Study Design
We conducted a model-based economic evaluation on the cost-effectiveness of interventions to prevent myopia progression in children.We compared the effect of low-dose atropine eye drops (0.05% and 0.01%), DIMS, outdoor activity, soft contact lenses (daily disposable soft contact lenses [MiSight; CooperVision] and multifocal soft contact lenses [MSCLs]), RGPCLs, PALs, BSLs, orthokeratology, HALs, and red light therapy with single-vision lenses (SVLs) for controlling myopia progression over a 5-year period.Single-vision lenses were chosen as the comparator because this is the traditional approach to manage myopia.We set a 5-year period because previous clinical trials involving myopia interventions usually did not exceed this period. 29The target population consisted probability (proportion of iterations) that a strategy was cost-effective over a willingness-to-pay (WTP) threshold range of US $0 to $10 000 per spherical equivalent refraction (SER) reduction or axial length (AL) reduction.Minimum and maximum values of effectiveness were derived as the range of 95% CIs of myopia reduction. 30We reported the methods and results of this study in accordance with the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) reporting guideline.

Model Design and Myopia Progression
A transition-state model was implemented in TreeAge Pro software, version 2022 (TreeAge Pro Healthcare) to simulate the effect of prescribed interventions on myopia progression and to monitor the transition between health states.We used a Markov model with low, moderate, and high myopia as the health states (eFigure 1 in Supplement 1).Low myopia was defined as the spherical equivalent of −0.50 to −2.99 diopters (D), moderate myopia as −3.00 to −5.99 D, and high myopia as −6.0 D or greater. 31,32Transition probabilities were calculated based on annual myopia progression rate (eMethods in Supplement 1).The annual myopia progression rates were obtained from randomized clinical trials (eTable in Supplement 1) and were categorized as slow (<0.5 D), intermediate (0.5 to 0.99 D), and rapid (Ն1.0 D) progression. 11,24,33In our model, the proportion of patients starting in each myopic state was based on the prevalence data reported by Yam et al, 34 assuming that patients would progress from the less serious myopic state to the more serious state.The risk of progressing from one state to another could be reduced by treatment.We also assumed that myopia progression was irreversible.Hence, once a patient develops a more severe myopic state, the patient cannot revert to a lower myopic state.Additionally, we assumed that myopia progression was directly related to myopic state; patients with low and high myopia would have slow and rapid myopia progression, respectively. 35,36In our model, contact lenses or spectacles were changed when patients progressed to high myopia.

Costs and Outcomes of Effectiveness
Analysis was performed from a societal perspective, including direct and indirect costs.Direct costs included costs of consultations, follow-up visits, optometric services (refraction), specialized ophthalmic services, spectacles, contact lens solutions, and medications.Indirect costs included costs of adverse events and caretakers' loss of productivity (time spent and wages lost in accompanying a child for interventions).Adverse events with the use of atropine eye drops were allergic conjunctivitis and photophobia requiring photochromatic glasses. 11Adverse events with the use of contact lenses consisted of bacterial keratitis, cornea infiltrates, allergies, hordeolum, and corneal staining. 37,38We assumed that patients spent a maximum of 2 hours in the clinic.Loss of productivity was calculated based on the median annual earnings from the Census and Statistics Department of Hong Kong. 39sts were determined based on the published charges of the Hospital Authority of Hong Kong, 40 the Chinese University of Hong Kong Eye Centre, and key informants.Except for patients given orthokeratology, spectacle lenses (DIMS, PALs, HALs, and BSLs), or contact lenses, all patients were assumed to wear SVLs and would at least incur the cost of spectacles.Hence, the baseline cost of outdoor activity was the cost of spectacles.Given that outdoor activity should otherwise have no direct cost, we investigated how our model would be affected if the cost was zero and if the cost included productivity losses related to spending time outdoors in sensitivity analysis.All costs were based on item costs in the year 2022, collected in Hong Kong dollars (HK $) and converted to US dollars (US $) at a rate of HK $7.85 per US $1. 41 All costs were discounted at an annual rate of 3% as recommended by the World Health Organization. 42e outcomes for effectiveness were defined in terms of the change in SER and AL over 1 year, determined from published meta-analysis from literature. 30,43The annual change in SER and AL for the untreated cohort was obtained from the placebo cohort of Yam et al. 11 Table 1 shows the model parameters.The main outcome of our study was the incremental cost-effectiveness ratio (ICER),

Results
Figure 1 and Table 2 show the results of the base-case analysis.The projected total cost of treating myopia progression over a 5-year time horizon was least for outdoor activities, with a total cost of HK $34 108 (US $4345).Over this period, orthokeratology was the most expensive, with a total cost of Additionally, we performed probabilistic sensitivity analysis to determine the optimum strategy at varying WTPs in a Monte Carlo simulation, using 1000 iterations (Figure 2 and eFigure 3 in

Discussion
To our knowledge, this economic evaluation is one of the first studies to demonstrate the costeffectiveness of interventions for myopia progression.We included 13 interventions, providing a comprehensive assessment of a wide range of interventions for myopia progression over a 5-year time horizon.Our results show that at higher WTP thresholds (HK $19 625 [US $2500]/SER reduction to HK $78 500 [US $10 000]/SER reduction), atropine, 0.05%, was the strategy most likely to be cost-effective, followed by HALs and red light therapy.Below this threshold, outdoor activity was the most likely cost-effective strategy.Our study provides information for policy makers in addressing myopia.
The iterations of atropine, 0.05%, to be cost-effective was about 40% at a WTP of HK $19 625 (US $2500)/SER reduction, compared with 25% for HALs and 8% for red light therapy.The iterations of red light therapy to be cost-effective increased as the WTP threshold increased.Although red light therapy could be cost-effective (29%) at higher WTP thresholds (HK $78 500 [US $10 000]/SER reduction), it is more costly than atropine, 0.05%.
In terms of AL, atropine, 0.05%, was the most likely cost-effective strategy at a WTP threshold of HK $27 475 (US $3500) and beyond.Below this threshold, outdoor activity remained the most likely cost-effective intervention.Orthokeratology was a dominant strategy in the base-case analysis, meaning it was more effective than the reference case strategy.However, atropine, 0.05%, was more likely to be cost-effective than orthokeratology in the probabilistic analysis, possibly due to the high costs associated with orthokeratology.
Outdoor activity was not associated with any significant cost and was the least expensive strategy, while contact lenses (orthokeratology, daily disposable contact lenses, MSCLs, and RGPCLs) were the most expensive strategies.In addition to the benefit of reducing myopia onset and progression in children, [46][47][48][49][50][51] outdoor activity also improves their general health and development, 52 reduces childhood obesity, 53 prevents chronic disease, and increases vitamin D levels for development of bones and teeth. 54,55Given these health benefits, measures to encourage and promote outdoor activities should be strongly advocated.Orthokeratology is associated with other difficulties such as the need for skills for contact lens fitting, the risk of infective keratitis, and pain.
These factors have limited the widespread use of orthokeratology. 25Although orthokeratology could be cost-effective, it requires strict monitoring due to the potential sight-threatening complications.

Conclusions
The findings of this economic evaluation suggest that atropine, 0.05%, and outdoor activity may be cost-effective approaches for controlling myopia progression in children.Though more expensive, red light therapy, HALs, and orthokeratology may also be cost-effective.The use of these interventions could help control myopia in a cost-effective way.

Table 2 .
Base-Case Cost-Effectiveness Results a Unit of measure is diopters for spherical equivalent refraction and millimeters for axial length.b Dominant strategies.Downloaded From: https://jamanetwork.com/ on 11/04/2023 44ditionally, the World Health Organization defines an intervention as highly cost-effective if it costs less than the per-capita gross domestic product (GDP) and as cost-effective if it costs less than 3 times the per capita GDP for a given country.42Inthisstudy, the ICERs of the spectacle optionsLimitationsOur study has some limitations.First, costs associated with interventions may have been underestimated.Even though we adapted a societal perspective, certain indirect costs (eg, cost of transportation) were not included in our analysis.Second, costs were calculated according to the charges of the Chinese University of Hong Kong Eye Centre.The results of our study may not be generalizable to other regions that do not have a similar economic setting as Hong Kong.It is worth noting that the costs involved may vary considerably in different regions.Third, we did not assess the impact of myopia interventions on quality of life.The use of orthokeratology compared with SVLs and soft contact lenses, as well as low-concentration atropine compared with SVLs, showed comparable effects on quality of life.45However, a reduction in myopia progression by 1 D could significantly affect future occurrence of pathologic myopia.44Becausemyopia interventions are intended to prevent progression to pathological myopia, effectiveness was assessed based on their capacity to reduce SER and AL.Fourth, the potential for rebound with myopia interventions has not been accounted for.Fifth, efficacy data were obtained from published meta-analyses, therefore treatment efficacy may vary between different regions; however, our sensitivity analyses accounted for these variations.Last, our model did not account for a pathological state of myopia.Pathologic myopia is a distinct condition that differs from regular myopia.The primary objective of interventions aimed at myopia progression is generally to reduce the progression of myopia, rather than treating the complications that are associated with pathologic myopia.Effective myopia progression interventions may not necessarily treat pathologic myopia complications.Moreover, limited data are available on the effect of myopia interventions on pathologic myopia because of the shorter duration of randomized clinical trials.Additionally, we modeled our study over a time horizon of 5 years, by which time a 10-year-old child (start age) would not have developed pathologic myopia.